Field of the Invention
The disclosure provides biodegradable amphiphilic liquid crystalline copolymers that can readily self-assemble to nanoparticles in aqueous solutions and also allow for encapsulation of hydrophobic pharmaceutically active molecules.
Description of the Related Art
Clinical use of drugs (e.g., anticancer drugs) is limited due to their hydrophobicity and non-specific toxicity. For example, the majority of clinically used anticancer drugs are low molecular compounds that diffuse rapidly though the body in both healthy and diseased tissue causing serious side effects. There is a growing need to develop safe and effective delivery systems for anticancer drugs. Self-assembled nanoparticle structures allow encapsulation of the anticancer drugs in the core while the hydrophilic shell allows for increased water solubility and stability. Nanoparticles with appropriate size and surface property may have opportunity to accumulate in tumor sites through the enhanced permeability and retention (EPR) effect, which results from abnormalities of tumor blood and lymphatic vasculature.
Various self-assembled nanoparticles have been developed for delivery of anticancer drugs. Unfortunately, most of these have not shown beneficial effects in clinical trials. The major obstacle for drug-delivery polymer systems is poor in vivo stability, low drug loading levels, reduced tumor targetability and slow drug release in tumor tissue and/or inside the tumor cells. Furthermore, many synthetic biodegradable copolymers upon erosion in vivo yield oligomers and monomers that adversely interact with the surrounding tissue.
Copolymers with cholesterol end-groups have also generated interest for various biomedical applications including serving as membranes for cell attachment and proliferation, forming the basis of polymeric scaffolds, and as materials with improved blood compatibility. But, reported amphiphilic polymer architectures that contain cholesterol are conjugates or linear copolymers with only one or a few cholesterol molecules. This results in low stability, limited drug loading capacity to 20% (w/w) with low encapsulation efficiency and fast drug release for these cholesterol-containing copolymers.
Redox-Sensitive nanocarriers containing disulfide bonds have received much attention for intracellular drug delivery due to the existence of a high glutathione (GSH) concentration in the tumor microenvironment and cancer cells. For instance, several groups have reported redox-sensitive polymer/DNA complexes, polyion complex micelles for siRNA delivery, crosslinked micelles, and degradable nanogels with good stability under the physiological conditions that, rapidly released encapsulated drugs in the intracellular reductive environment. However, limited information is available on the in vivo behavior of nanoparticles comprised of reductive-sensitive polymers and the interaction between the nanoparticles and tumor tissue.